13-31758273-A-G

Variant names:

• chr13-31758273-A-G
• rs764255499
• NM_130806.5:c.110A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130806.5(RXFP2):​c.110A>G​(p.Gln37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q37P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RXFP2 NM_130806.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

Genes affected

RXFP2 (HGNC:17318): (relaxin family peptide receptor 2) This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12526962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.110A>G	p.Gln37Arg	missense_variant	Exon 2 of 18	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.110A>G	p.Gln37Arg	missense_variant	Exon 2 of 17		NP_001159530.1
RXFP2	XM_017020389.2	c.110A>G	p.Gln37Arg	missense_variant	Exon 2 of 15		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.110A>G	p.Gln37Arg	missense_variant	Exon 2 of 18	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.110A>G	p.Gln37Arg	missense_variant	Exon 2 of 17	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.37
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.15
Sift	Benign	0.29	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0	.;B
Vest4		0.24
MutPred		0.41		Gain of catalytic residue at S39 (P = 0);Gain of catalytic residue at S39 (P = 0);
MVP		0.69
MPC		0.19
ClinPred		0.066	T
GERP RS		3.1
Varity_R		0.070
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs764255499; hg19: chr13-32332410;